Atherosclerosis is the underlying cause of most cardiovascular disease and considerable evidence supports the role of hypercholesterolemia as a risk factor for this disease. In preliminary work, we found that tertiary-butyl hydroquinone (TBHQ), at a dose lower than approved for human use, was effective in reducing plasma levels of both total cholesterol and triglycerides in a rat model. TBHQ is phenolic antioxidant commonly used as a food preservative. A patent, "Method for Reducing Blood Cholesterol and/or Blood Triglycerides," was subsequently obtained. The long-term objective of this research proposal is to determine the antiatherogenic potential of TBHQ and advance its commercial development. Our specific aims are to test the efficacy of TBHQ in: (1) reducing aortic atherosclerosis; (2) lowering plasma lipid levels; (3) promoting a less atherogenic lipoprotein profile and; (4) reducing plasma levels of C-reactive protein (CRP). Elevated levels of CRP are a risk factor for cardiovascular disease. In our phase I experiments, we will use the apoE knockout (apoE-/-) mouse model since it has been extensively used to study the antiatherogenic potential of other phenolic antioxidants. Our preliminary market analysis suggests that TBHQ could have a potential market of $100 million per year as a lipid-lowering agent. Commercial development should be accelerated since NIH has already conducted extensive toxicological studies with TBHQ.